Astroviruses are small, non-enveloped viruses with a single-stranded positive-sense RNA genome, causing acute gastroenteritis in children and immunocompromised patients. Since positive-sense RNA viruses have been frequently found to replicate associated to membranous structures, in this work we characterized the replication of the human astroviruses serotype 8 strain Yuc8 in Caco-2 cells, using density gradient centrifugation and free flow zonal electrophoresis (FFZE) to fractionate cellular membranes. Structural and nonstructural viral proteins, positive- and negative-sense viral RNA, and infectious virus particles, were found to be associated with a distinct population of membranes separated by FFZE. The cellular proteins associated with this membrane population in infected and mock-infected cells, were identified by tandem mass spectrometry. Results indicated that membranes derived from multiple cell organelles were present in the population. Gene ontology and protein-protein interaction network analysis showed that groups of proteins with roles in fatty acid synthesis and ATP biosynthesis were highly enriched in the fractions of this population in infected cells. Based on this information, we investigated by RNA interference the role that some of the identified proteins might have in the replication cycle of the virus. Silencing the expression of genes involved in cholesterol (DHCR7, CYP51A1) and fatty acid (FASN) synthesis, phosphatidylinositol (PI4KIII-β) and inositol-phosphate (ITPR3) metabolism, and RNA helicase activity (DDX23), significantly decreased amounts of Yuc8 genomic and antigenomic RNA, synthesis of the structural protein VP90, and virus yield. These results strongly suggest that astrovirus RNA replication and particle assembly take place in association with modified membranes potentially derived from multiple cell organelles.
Astroviruses are common etiological agents of acute gastroenteritis in children and immunocompromised patients. More recently, they have been associated with neurological diseases in mammals, including humans, and are also responsible for different pathologies in birds. In this work we provide evidence that astrovirus RNA replication and virus assembly occurs in contact with cell membranes potentially derived from multiple cell organelles and show that cellular proteins involved in lipid metabolism that associate with these membranes are required for the efficient viral replication. Our findings provide information to the knowledge of astrovirus biology and provide information that might be useful to develop therapeutic interventions to prevent virus replication.
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 March 2025.
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#7,960,052
of 25,374,647 outputs
Outputs from Journal of Virology
#10,485
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#85,807
of 275,662 outputs
Outputs of similar age from Journal of Virology
#96
of 229 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 25,689 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.5. This one has gotten more attention than average, scoring higher than 57% of its peers.
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We're also able to compare this research output to 229 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 56% of its contemporaries.
